Esters of polyhydroxy-benzoic acids and method for their preparation



Patented May 6, 1952 ESTERS OF POLYHYDROXY-BENZOIC ACIDS AND METHOD FORTHEIR PREPARATION Waldo C. Ault, Philadelphia, George C. Nutting,Abington, and James K. Weil, Lansd-ale, Pa., assignors to the. UnitedStates of America as represented by the Secretary of Agriculture NoDrawing. Application April 22, 1947, SerialNo. 743,210

(Granted under the act of March 3, 1883, as amended April'30, 1928; 370O. G. 757) 18 Claims.

This application is made under the act of March 3, l883, as amended bythe act of April 30, 1928., and the invention herein described, ifpatented, may be manufactured and used by or for the Government of theUnited States of America for governmental purposes without the paymentto us of any royalty thereon.

This invention relates to esters of polyhydroxybenzoic acids and moreparticularly to the esters of these acids with aliphatic alcoholscontaining more than six carbon atoms per molecule and theirpreparation.

Esters of gallic acids with lower fatty alcohols can be obtained bydirect esterification, frequently on heating the reactants in thepresence of suitable esterification catalysts. When this procedure isfollowed in an attempt to esterify gallic acid with higher fattyalcohols containing more than six carbon atoms per molecule, theesterification either does not take place, or the corresponding estersare formed in such small amount that it is not feasible to isolate themfrom the reaction products. Similar results are obtained on heating thereactants with inert non-polar solvents such as benzene, toluene,cumene, or

other non-polar organic solvents commonly utltheir application forPatent Serial No. 678,188,

filed June 21, 1546, that alkyl esters of gallic acid and of some otherpolyhydroxy-benzoic acids can be prepared by esterification-of thecorrespond ing benzyloXy-derivatives of benzoic acid and su sequentdebenzylation of the resulting ester by catalytic hydrogenation. Ourmethod, however, is also applicable to the production ofpolyhydroXy-benzoic acid esters of oleiinic alcohols, since it obviatesthe hydrogenation step, which causes addition of hydrogen to the doublebond of the alcohol radical and thus converts it to the correspondingalkyl group.

An object of this invention is the production of polyhydroxy-hcnzoicacid esters of higher aliphatic alcohols by methods that are simpler andmore economical than those used heretofore. A further object is theprovision of a method for producing polyhydroXy-benzoic acid esters ofaliphatic alcohols containing more than six carbon atoms per molecule,by direct esteriiication. Another object is to provide new compositionsof matter which are polyhydroXy-benzoic acid esters. of alcoholscontaining more. than six. carbo'ns per molecule, in particular,unsaturated a1.-

cohols. Other objects and advantages of the invention will appearhereinafter.

We have found that esters of polyhydroxybenzoic acids with aliphaticalcohols containing more than six carbon atoms per molecule are formedby direct esterification in the presence of a polar organic solvent. Inaccordance with the method of our invention the polyhydroxy-benzoic acidis heated with the aliphatic alcohol. in the presence of'a polar organicsolvent, and preferably in the presence of an esterification catalyst,at a temperature and for the length of time suificient to causeformation of the ester.

The method of this invention is applicable to polyhydroXy-benzoic acidscontaining hydroxyl groups in para and/or meta positions to. thecarboXyl group, such as gallic acid, p-rotocatechuic acid, andalpha-resorcylic acid. Aliphatic alcohols suitable for effectingesterification of these acids include saturated and unsaturated alcoholscontaining more than six carbon atoms per molecule, for instance n-octylalcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearylalcohol, and. oleyl alcohol. Suitable polar organic solvents are polarorganic solvents which under the conditions of the process arechemically inert toward the reactants and reaction products. Such polarsolvents include for example, nitrobenzene, ortho-dichlorobenzene,anisole and phenetole, which can be used singly or in combination.Addition of esterification catalysts,

such as sulfuri acid, toluene sulfonic acid, naphthalene sulfonic acid,or nitrobenzene sulfonic acid and similar acidic substances increasesthe reaction rate of the esterification process.

The expression polar solvents is employed here in its widely acceptedsense. The following publications indicate the meaning of the term,being the widely accepted manner of defining such solvents:

Liquids, for the sake of convenience are generally divided intotwoclasses, polar and nonpolar The dielectric constant of a compound is oneof the best measures of polarity." Lewis, Squires and Broughton,Industrial Chemistry of Colloidal and Amorphous Materials. 1942, page15.

Many organic solvents exhibit this [electrical] conductivity. hosesubstances are chemically active and are referred to as polar solventsSolvents like alcohols and ketones, have high dielectric constants andthis is evidence of strong polarity. Those of low dielectric constants,like the, aliphatic and aromatic hydrocarbons, are classified asnonpolar solvents. Mellan, Industrial Solvents, 1939, page 9.

The dielectric constants of the solvents mentioned in the applicationand of some common inert, non-polar solvents, boiling within the rangeclaimed are listed in the following table:

Since esterification proceeds more rapidly at higher temperature and isfacilitated by removal of water from the reaction mixture it is usuallyadvantageous to utilize polar solvents boiling above 100 C. and toconduct the reaction under reflux with concurrent separation of water.Since the reaction temperature must not, however, be sufliciently highto cause any appreciable decomposition of the polyhydroxy-benzoic acid,the operator should determine the optimum upper limit in each case. Thusfor example, esterification of gallic acid in the presence ofnitrobenzene is best effected by conducting the reaction under refluxand using a mixture of nitrobenzene with a lower boiling polar solventthereby maintaining the reaction mixture at a temperature below thedecomposition temperature of gallic acid. The ratio of reactants tosolvent may be varied within wide limits. We have found, however, thatwhen the polar solvent consists of a mixture of nitrobenzene withanother polar organic solvent the highest yields of esters may beobtained if the amounts of polyhydroxy-benzoic acid and nitrobenzenepresent in the reaction mixture approximate the molar ratio of 1 to 1.

The esters of polyhydroxy-benzoic acids with aliphatic alcoholscontaining more than six carbon atoms are useful as antioxidants andrancidity inhibitors for fatty and oily materials and as intermediatesin production of synthetic chemicals.

As illustrative embodiments of a manner in which our invention may becarried out in practice the following examples are given.

Example I temperature, washed with water to remove the catalyst andunreacted gallic acid, and the solvent evaporated under reducedpressure. Recrystallization of the distillation residue frombenzene-petroleum ether gave 8.8 grams (52 percent of theory) of dodecylgallate melting at 96-97 C.

Example II Cetyl gallate.5.64-. grams of gallic acid, 7.27 grams ofcetyl alcohol, 0.5 gram of beta-naphthalene sulfonic acid and cc. ofnitrobenzene were refluxed as described in Example I. Sincediscoloration of the mixture gave reason to be lieve that somedecomposition of gallic acid was taking place, 50 cc. ofo-dichlorobenzene was added at the end of the first half hour andrefluxing was continued for an additional 17 hours.

Three grams (24 percent of theory) of hexadecyl gallate melting at 96-98C. was recovered from the reaction mixture by the procedure described inExample I. On further recrystallization from benzene-petroleum ether,this product yielded 2.6 grams of ester having a melting point of 98-99C.

A somewhat lower yield of hexadecyl gallate was obtained on heating amixture of 5.64 grams gallic acid, 7.27 grams cetyl alcohol, 0.5 grambeta-naphthalene sulfonic acid and 100 cc. nitrobenzene at 170 C. for 24hours, and treating the resulting reaction mixture as described inExample I. The temperature was kept constant by maintaining a pressuresomewhat below at mospheric.

Example III Oleyl gallate.4.71 grams of gallic acid, 8.93 grams of oleylalcohol, 0.5 gram of p-toluene sulfonic acid and 150 cc. ofo-dichlorobenzene were refluxed for 29 hours during which time anadditional 0.4 gram of p-toluene sulfonic acid was added by increments.

The mixture was allowed to cool to room temperature and filtered. 2.36grams of unreacted gallic acid was thus recovered. The filtrate was thenwashed three times with equal volumes of hot water. Theo-dichlorobenzene was removed by distillation under vacuum and theresidue taken up in a mixture of benzene and petroleum ether from whichthe ester was allowed to crystallize. Approximately 1 gram ofcrystalline octadecenyl gallate melting at 83-85f C. was obtained whichafter crystallization gave a crystalline material, M. P. 85.f5-86.5 C.Similar results were obtained when a mixture of cc. 0- dichlorobenzeneand 5 cc. of nitrobenzene was used as the solvent mixture.

Example IV Lauryl yallate.-A mixture of 3.6 grams of gallic acid, 8grams n-dodecyl alcohol, 0.2 gram naphthalene beta-sulfonic acid, 45cc.anisole and 2.2 cc. nitrobenzene was refluxedfor 15 hours. The ester wasrecovered as described" in Example IV and recrystallized frombenzene-petroleum ether-mixturez 5.5 grams (7'? percent) of dodecylgallate, M. P. 96.5-97.0 C; was obtained. An additional 4grams of crudeester (M. P. 85) crystallized from the mother liquor.

Example: VI

Lauryl gaZlate.-A mixture of 51 grams gallic acid, 112 grams. laurylalcohol, 2.5 grams naphthalene beta-sulfonic acid, 535 cc. anisole and31 cc. nitrobenzene was refluxed for hours. 67.8 grams (66.8 percent) ofdodecyl. gallate, M. P. 96-97 C. was recovered by the procedure given inExample V.

Example VII Myristyl gaZZate;A mixture of 3 grams gallic acid, 7.5 gramsmyristyli alcohol, 0.2 gram naphthalene-beta-sulfonic acid, cc.phenetole and 2.2 cc. nitrobenzene was refluxed for 9 hours. Thev esterrecovered as in Example IV was recrystallized from benzene-petroleumether yielding 2.6 grams (41 percent) of tetradecyl gallate, M. P. 983C.

Example VIII Cetyl galleria-A mixture of 3.4 grams gallic acid, 9.6grams cetyl alcohol, 0.2 gram naphthalene-beta-sulfonic acid, 40 cc.anisole and 2.1 cc. nitrobenzene was refluxed for 15 hours. The esterrecovered as in Example IV was recrystallized to yield 2.1 grams (27percent) of hexadecyl gallate, M. P. 93-94 C.

Example IX Octodecyl gallate was prepared by reacting 3.4 grams ofgallic acid with 11.4 grams of l-octadecanol according to the proceduredescribed in Example VIII. The yield was 7.2 grams (86 percent) of crudeoctadecyl gallate, M. P. 9l93 C. A purified ester melting at 101.5-l03.5C. was obtained by recrystallization.

Example X Lauryl protocatechuate.A mixture of 0.9 gram protocatechuicacid, 2.6 grams lauryl alcohol, 0.05 gram naphthalene-beta-sulfonicacid, 20 cc. anisole and 0.7 gram nitrobenzene was refluxed for '7hours. zoate, M. P. 102.'7-103.6 C. was recovered from th reactionmixture by a procedure analogous to those described in the foregoingexamples. The yield was 0.9 gram (4'7 percent of the calculated).

Example XI Lauryl alpha-resorcylate, M. P. 8689i C. was obtained byreacting 3,5-dihydroxybenzoic acid with lauryl alcohol, according to theprocedure described in Example X.

Example XII Dodecyl-3, 4-dihydroxyben- Having thus described ourinvention, we claim: 1. A process of producing an ester'of' a.polyhydroxybenzoic' acid of; the general formula:

COOH

in whicha: is an integer from.2.to 3 and in which the positions ortho tothe carboxyl group are free of substituents; comprising heating saidacid with an alcohol of the formula RCH2OH, in which R is a radicaltaken from the group consisting of olefine and saturated alkyl radicalshaving more than five carbon atoms, said heating being in the presenceof an acid esterification catalyst and under reflux and return ofsolvent with concurrent separation of water, thesolvent being a polarorganic solvent medium which under the conditions of the process ischemically inert toward the reactants and the reaction products andwhich boils above C. and not higher than the boiling point ofnitrobenzene, andbelow the decomposition temperature of thepolyhydroxy-benzoic acid, the solvent medium being a substitutedhydrocarbon taken from the group consisting of nitrobenzene,ortho-dichlorbenzen anisole, and phenetole.

2. The process described in claim 1 in which thethe solvent medium is amixture of nitrobenzene and another solvent of said group, thenitrobenzene being present in the reaction in A minor amount withrespect to the said solvent,

and recovering the ester of the acid and the alcohol.

3. The process defined in claim 1 in which the acid is gallic acid.

The process defined in claim 1 in which the acid is protccatechuic acid.

5. The process defined in claim 1 in which the acid is 3,5-dihydroxybenzoic acid.

6. The process defined in claim 1 in which the alcohol is a normalsaturated aliphatic alcohol containing from 8 to 18 carbon atoms permolecule.

7. The process defined in claim 1 in which the alcohol is oleyl alcohol.

8. The process defined in claim 1 in which the alcohol is laurylalcohol.

9. The process defined in claim 1 in which the alcohol is n-cctadecylalcohol.

10. The process of preparing oleyl gallate com- I prising heating toreflux oleyl alcohol with gallic acid in a medium ofortho-dichlorobenzene in the presence of minor amounts of nitrobenzenewith respect to the weight of the gallic acid.

11. The process described in claim 10 in which the reaction is in thepresence of p-toluene sulfonic acid.

12. A process comprising refluxing a mixture of protocatechuic acid,lauryl alcohol, anisole and nitrobenzene, and recovering laurylprotocatechuate from the reaction mixture, the anisole being in molarexcess with respect to the protocatechuic acid, the nitrobenzene beingin minor amount with respect to the anisole.

13. A process of producing an ester of a polyhydroxy-benzoic acid of theformula:

(IJOOH in which x is an integer from 2 to 3 and in which the positionsortho to the carbcxyl group are free of substituents; comprising heatingsaid acid with an alcohol of the formula RCH2OH, in which R is a radicaltaken from the group consisting of olefine and saturated alkyl radicalshaving more than five carbon atoms, said heating being under reflux in amixture of nitrobenacne and anisole.

14. The process described in claim 1 in which the solvent medium is amixture of nitrobenzene and another solvent of said group having aboiling point below nitrobenzene, the molar ratio of polyhydroxybenzoicacid to nitrobenzene being about 1 to 1.

15. The process described in claim 1 in which the solvent medium is amixture of nitrobenzene and another solvent of said group having aboiling point below nitrobenzene.

16. The process described in c1aim l in which the solvent is a mixtureof nitrobenzene and anisole.

17. The process described in claim 1 in which the polyhydroxybenzoicacid is taken from the group consisting of gallic acid, protocatechuicacid, and 3,5-dihydroxy benzoic acid, the alcohol being taken from thegroup consisting of oleyl, lauryl, n-octyl, myristyl, cetyl, andstearyl.

18. The process of claim 1 in which the alcohol is monohydric.

WALDO C. AULT. GEORGE C. NUTTING. JAMES K. WEIL.

8 REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS OTHER REFERENCES Steward G. Morris et al.: J. Am.Chem. Soc., vol. 68, pp. 500-501.

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Organic Preparation, 1945, pp.

1. A PROCESS OF PRODUCING AN ESTER OF A POLYHYDROXYBENZOIC ACID OF THEGENERAL FORMULA: